ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.907G>A (p.Gly303Arg) (rs142808899)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biochemistry Laboratory of CDMU,Chengde Medical University RCV000180217 SCV000899187 pathogenic Smith-Lemli-Opitz syndrome no assertion criteria provided case-control
Counsyl RCV000180217 SCV000485874 likely pathogenic Smith-Lemli-Opitz syndrome 2016-02-25 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724095 SCV000232612 pathogenic not provided 2017-10-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000180217 SCV000914537 likely pathogenic Smith-Lemli-Opitz syndrome 2018-12-13 criteria provided, single submitter clinical testing The DHCR7 c.907G>A (p.Gly303Arg) missense variant has been reported in five studies in which it is found in a compound heterozygous state in six individuals with Smith-Lemli-Opitz syndrome (Matsumoto et al. 2005; Ko et al. 2010; Lee et al. 2010; Oh et al. 2014; Tamura et al. 2017). Five of the individuals inherited the variant from one of their unaffected carrier parents; the genotype of the sixth individual's parents is not available. The p.Gly303Arg variant was absent from 184 control chromosomes and is reported at a frequency of 0.00068 in the African American population of the Exome Sequencing Project. The p.Gly303Arg variant is located within the seventh transmembrane domain, which is a highly conserved sterol-sensing domain. Based on the evidence, the p.Gly303Arg variant is classified as likely pathogenic for Smith-Lemli-Opitz syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000180217 SCV000931749 pathogenic Smith-Lemli-Opitz syndrome 2018-09-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 303 of the DHCR7 protein (p.Gly303Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs142808899, ExAC 0.05%). This variant has been observed in several patients and families affected with DHCR7-related conditions (PMID: 16044199, 28503313, 20052364). ClinVar contains an entry for this variant (Variation ID: 198773). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000180217 SCV000267288 uncertain significance Smith-Lemli-Opitz syndrome 2016-03-18 criteria provided, single submitter reference population

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